Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. @*Materials and Methods@#Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. @*Results@#We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. @*Conclusion@#This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

Analysis of Proliferation Characters of Bone Marrow Mesenchymal Stem Cells Derived from Patients with Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To analyze the proliferation potential of bone marrow-derived mesenchymal stem cells (MSC) in patients with myelodysplastic syndrome (MDS).@*METHODS@#The MSC derived from the 24 patients with newly diagnosed MDS (MDS-MSC group) and MSC derived from 15 patients with nutritional anemia (control group) in the Affiliated Hospital of Hebei University were used as the research objects. The proliferation potential of MSC was analyzed by colony-forming unit assay, doubling time, cumulative passaging, cell number after 10 days of culture with equal amount of MSC and MTT experiment. The mechanism of abnormal proliferation was analyzed by cell cycle experiment, apoptosis experiment and p21 gene expression assay.@*RESULTS@#In the colony forming unit assay, the number of MDS-MSC colonies was 4.44±2.51, which was significantly lower than that of the control group (12.44±2.55)(P<0.01); the doubling time of MDS-MSC group was significantly longer than that of the control group (7.80±3.26 vs 3.63±0.85) (P<0.01); the number of MDS-MSC in 5×10@*CONCLUSION@#The proliferative capability of MDS-MSC is significantly reduced, which relates with the arrest of cell cycle in G

Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. @*Materials and Methods@#Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. @*Results@#We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. @*Conclusion@#This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.